Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate → HCID 57546004, compound

HRID 913978Notes

Reaction equation

HRID 913978 reaction equation
ClC(Cl)(Cl)C(=N)O[CH:5]([C:7]1[C:15]2[N:14]=[CH:13][N:12]([CH2:16][CH3:17])[C:11]=2[CH:10]=[C:9]([C:18]([F:21])([F:20])[F:19])[CH:8]=1)[CH3:6].[OH:25][CH2:26][C:27]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.ClC(Cl)C.C1CCCCC1>>[CH2:16]([N:12]1[C:11]2[CH:10]=[C:9]([C:18]([F:21])([F:19])[F:20])[CH:8]=[C:7]([CH:5]([O:25][CH2:26][C:27]3([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[CH3:6])[C:15]=2[N:14]=[CH:13]1)[CH3:17]

Participants

4

Reactant 3

HCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 21916605HCID 21916605, compoundHCID 57546123HCID 57546123, compound

Product 1

HCID 57546004HCID 57546004, compound

Conditions

Temperature
0 °C

Procedure

(±)-(1-(1-Ethyl-6-(trifluoromethyl)-1H-benzo[d]imidazol-4-yl)ethyl 2,2,2-trichloroacetimidate (670 mg, 1.664 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (727 mg, 2.496 mmol) were combined in a dichloroethane/cyclohexane mixture (4:2, 6 mL) and cooled to 0° C. The reaction mixture was treated with tetrafluoroboric acid-diethyl ether complex (91 μL, 0.67 mmol), and subsequent processing including extractive work up and purification were carried out as described in example 8 to give 274 mg (30.7%) as white foam-like solid. 1H-NMR (500 MHz, CHLOROFORM-D) δ ppm 7.97 (s, 1 H), 7.54 (s, 1 H), 7.29-7.37 (m, 5 H), 7.16-7.24 (m, 1 H), 5.11 (q, J=6.4 Hz, 1 H), 4.20-4.29 (m, 2 H), 3.64-3.80 (m, J=13.1 Hz, 2 H), 3.29-3.37 (m, 2 H), 2.93-3.10 (m, 2 H), 2.09-2.22 (m, 2 H), 1.87-2.03 (m, 2 H), 1.56 (t, 3 H), 1.39-1.48 (m, 12 H). 532.40 (MH)+.

Workup

  1. additionThe reaction mixture was treated with tetrafluoroboric acid-diethyl ether complex (91 μL, 0.67 mmol), and subsequent processing
  2. custompurification
  3. customto give 274 mg (30.7%) as white foam-like solid

Sources & evidence

ORD record
ord-fcb4bb9d252546a4906cf7e395b136e5
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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